Temporal Risk of Nonfatal Cardiovascular Events After Chronic Obstructive Pulmonary Disease Exacerbation: A Population-based Study.

Rationale: Cardiovascular events after chronic obstructive pulmonary disease (COPD) exacerbations are recognized. Studies to date have been post hoc analyses of trials, did not differentiate exacerbation severity, included death in the cardiovascular outcome, or had insufficient power to explore individual outcomes temporally.Objectives: We explore temporal relationships between moderate and severe exacerbations and incident, nonfatal hospitalized cardiovascular events in a primary care-derived COPD cohort.Methods: We included people with COPD in England from 2014 to 2020, from the Clinical Practice Research Datalink Aurum primary care database. The index date was the date of first COPD exacerbation or, for those without exacerbations, date upon eligibility. We determined composite and individual cardiovascular events (acute coronary syndrome, arrhythmia, heart failure, ischemic stroke, and pulmonary hypertension) from linked hospital data. Adjusted Cox regression models were used to estimate average and time-stratified adjusted hazard ratios (aHRs).Measurements and Main Results: Among 213,466 patients, 146,448 (68.6%) had any exacerbation; 119,124 (55.8%) had moderate exacerbations, and 27,324 (12.8%) had severe exacerbations. A total of 40,773 cardiovascular events were recorded. There was an immediate period of cardiovascular relative rate after any exacerbation (1-14 d; aHR, 3.19 [95% confidence interval (CI), 2.71-3.76]), followed by progressively declining yet maintained effects, elevated after one year (aHR, 1.84 [95% CI, 1.78-1.91]). Hazard ratios were highest 1-14 days after severe exacerbations (aHR, 14.5 [95% CI, 12.2-17.3]) but highest 14-30 days after moderate exacerbations (aHR, 1.94 [95% CI, 1.63-2.31]). Cardiovascular outcomes with the greatest two-week effects after a severe exacerbation were arrhythmia (aHR, 12.7 [95% CI, 10.3-15.7]) and heart failure (aHR, 8.31 [95% CI, 6.79-10.2]).Conclusions: Cardiovascular events after moderate COPD exacerbations occur slightly later than after severe exacerbations; heightened relative rates remain beyond one year irrespective of severity. The period immediately after an exacerbation presents a critical opportunity for clinical intervention and treatment optimization to prevent future cardiovascular events.

Cluster randomised controlled trial of specialist-led integrated COPD care (INTEGR COPD).

OBJECTIVE: Studies in hospital settings demonstrate that there is greater guideline adherence when care is delivered by a respiratory specialist, however, this has not been explored in primary care. The aim of this study is to determine the impact integrating respiratory specialists into primary care has on the delivery of guideline adherent chronic obstructive pulmonary disease (COPD) care. METHODS: 18 general practitioner (GP) practices were randomised to provide either usual or specialist-led COPD care. Patients at participating practices were included if they had an existing diagnosis of COPD. Outcomes were measured at the individual patient level. The primary outcome was guideline adherence, assessed as achieving four or more items of the COPD care bundle. Secondary outcome measures included quality of life, number of exacerbations, number of COPD-related hospitalisations and respiratory outpatient attendances. RESULTS: 586 patients from 10 practices randomised to the intervention and 656 patients from 8 practices randomised to the control arm of the study were included. The integration of respiratory specialists into GP practices led to a statistically significant (p<0.001) improvement in the provision of guideline adherent care when compared with usual care in this cohort (92.7% vs 70.1%) (OR 4.14, 95% CI 2.14 to 8.03). CONCLUSION: This is the first study to demonstrate that guideline adherence is improved through the integration of respiratory specialists into GP practices to deliver annual COPD reviews. To facilitate changes in current healthcare practice and policy, the findings of this paper need to be viewed in combination with qualitative research exploring the acceptability of specialist integration. TRIAL REGISTRATION NUMBER: NCT03482700.

Quantifying sustained health system benefits of primary care-based integrated disease management for COPD: a 6-year interrupted time series study.

BACKGROUND: Severe exacerbation of chronic obstructive pulmonary disease (COPD) is a trajectory-changing life event for patients and a major contributor to health system costs. This study evaluates the real-world impact of a primary care, integrated disease management (IDM) programme on acute health service utilisation (HSU) in the Canadian health system. METHODS: Interrupted time series analysis using retrospective health administrative data, comparing monthly HSU event rates 3 years prior to and 3 years following the implementation of COPD IDM. Primary outcomes were COPD-related hospitalisation and emergency department (ED) visits. Secondary outcomes included hospital bed days and all-cause HSU. RESULTS: There were 2451 participants. COPD-related and all-cause HSU rates increased in the 3 years prior to IDM implementation. With implementation, there was an immediate decrease (month 1) in COPD-related hospitalisation and ED visit rates of -4.6 (95% CI: -7.76 to -1.39) and -6.2 (95% CI: -11.88, -0.48) per 1000 participants per month, respectively, compared with the counterfactual control group. After 12 months, COPD-related hospitalisation rates decreased: -9.1 events per 1000 participants per month (95% CI: -12.72, -5.44) and ED visits -19.0 (95% CI: -25.50, -12.46). This difference nearly doubled by 36 months. All-cause HSU also demonstrated rate reductions at 12 months, hospitalisation was -10.2 events per 1000 participants per month (95% CI: -15.79, -4.44) and ED visits were -30.4 (95% CI: -41.95, -18.78). CONCLUSIONS: Implementation of COPD IDM in a primary care setting was associated with a changed trajectory of COPD-related and all-cause HSU from an increasing year-on-year trend to sustained long-term reductions. This highlights a substantial real-world opportunity that may improve health system performance and patient outcomes.

Do pulmonary rehabilitation programmes improve outcomes in patients with COPD posthospital discharge for exacerbation: a systematic review and meta-analysis.

INTRODUCTION: Previous systematic reviews have provided heterogeneous and differing estimates for the efficacy of pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease (COPD). The aim of this review was to examine the efficacy of pulmonary rehabilitation programmes initiated within 3 weeks of hospital discharge following an exacerbation of COPD. METHODS: An update of a previous Cochrane review was undertaken using the Cochrane Airways Review Group Specialised Register. Searches were conducted from October 2015 to August 2023 for studies that initiated pulmonary rehabilitation within 3 weeks of hospital discharge. Studies assessing the impact of solely inpatient pulmonary rehabilitation were excluded. Forest plots were generated using a generic inverse variance random effects method. RESULTS: Seventeen studies were included. Posthospital discharge pulmonary rehabilitation reduced hospital re-admissions (OR 0.48, 95% CI 0.30 to 0.77, I2=67%), improved exercise capacity (6 min walk test, mean difference (MD) 57 m, 95% CI 29 to 86, I2=89%; incremental shuttle walk test, MD 43 m, 95% CI 6 to 79, I2=81%), health-related quality of life (St. George's Respiratory Questionnaire, MD -8.7 points, 95% CI -12.5 to -4.9, I2=59%; Chronic Respiratory Disease Questionnaire (CRQ)-emotion, MD 1.0 points, 95% CI 0.4 to 1.6, I2=74%; CRQ-fatigue, MD 0.9 points, 95% CI 0.1 to 1.6, I2=91%), and dyspnoea (CRQ-dyspnoea, MD 1.0 points, 95% CI 0.3 to 1.7, I2=87%; modified Medical Research Council Dyspnoea Scale, MD -0.3 points, 95% CI -0.5 to -0.1, I2=60%). Significant effects were not observed for CRQ-mastery, COPD assessment test, EuroQol-5 Dimension-5 Level and mortality. No intervention-related adverse events were reported. DISCUSSION: Pulmonary rehabilitation delivered posthospital discharge for exacerbation of COPD results in a reduction in hospital re-admissions and improvements in exercise capacity, health-related quality of life and dyspnoea in the absence of any intervention-related adverse events. TRIAL REGISTRATION NUMBER: CRD42023406397.

Long-acting B-2 agonists (LABA) or long-acting muscarinic antagonists (LAMA): which one may be the first option in group A COPD patients?

INTRODUCTION: Long-acting muscarinic antagonists (LAMA) or beta-2 agonists (LABA) have been recommended for symptom control in group A COPD patients as a first-line bronchodilator treatment in GOLD guidelines. However, there is no mention of priority/superiority between the two treatment options. We aimed to compare the effectiveness of these treatments in this group. METHODS: The study cohort was formed of all subjects from six pulmonology clinics with an initial diagnosis of COPD who were new users of a LAMA or LABA from January 2020 to December 2021. Seventy-six group A COPD patients, in whom LABA or LAMA therapy had been started in the last 1 month as a first-line treatment, were included in our study. Participants were evaluated with spirometry, COPD Assessment Test (CAT), mMRC scale, and St. George Respiratory Questionnaire (SGRQ) for three times (baseline, 6-12th months). RESULTS: There were 76 group A COPD patients with LAMA (67.1%) and LABA (32.9%). The number of patients who improved in CAT score at the end of the first year was significantly higher in patients using LAMA than those using LABA (p = 0.022); the improvement at minimum clinically important difference (MCID) in CAT score of LAMA group at 1st year was also significant (p = 0.044). SGRQ total and impact scores were found to be statistically lower at 1st year compared to baseline in patients using LAMA (p = 0.010 and 0.006, respectively). Significant improvement was detected in CAT and SGRQ scores at the 6th month visit in the LAMA group having emphysema (p = 0.032 and 0.002, respectively). CONCLUSION: According to significant improvements in CAT and SGRQ score, LAMA may be preferred over LABA as a bronchodilator agent in group A COPD patients, especially in emphysema-dominant phenotype.

Predictors of reoperation after lung volume reduction surgery.

OBJECTIVES: Lung volume reduction surgery (LVRS) has proven an effective treatment for emphysema, by decreasing hyperinflation and improving lung function, activity level and reducing dyspnoea. However, postoperative air leak is an important complication, often leading to reoperation. Our aim was to analyse reoperations after LVRS and identify potential predictors. METHODS: Consecutive single-centre unilateral VATS LVRS performed from 2017 to 2022 were included. Typically, 3-5 minor resections were made using vascular magazines without buttressing. Data were obtained from an institutional database and analysed. Multivariable logistic regression was used to identify predictors of reoperation. Number and location of injuries were registered. RESULTS: In total, 191 patients were included, 25 were reoperated (13%). In 21 patients, the indication for reoperation was substantial air leak, 3 patients bleeding and 1 patient empyema. Length of stay (LOS) was 21 (11-33) vs. 5 days (3-11), respectively. Only 3 injuries were in the stapler line, 13 within < 2cm and 15 injuries were in another site. Multivariable logistic regression analysis showed that decreasing DLCO increased risk of reoperation, OR 1.1 (1.03, 1.18, P = 0.005). Resections in only one lobe, compared to resections in multiple lobes, were also a risk factor OR 3.10 (1.17, 9.32, P = 0.03). Patients undergoing reoperation had significantly increased 30-day mortality, OR 5.52 (1.03, 26.69, P = 0.02). CONCLUSIONS: Our incidence of reoperation after LVRS was 13% leading to prolonged LOS and increased 30-day mortality. Low DLCO and resections in a single lobe were significant predictors of reoperation. The air leak was usually not localized in the stapler line.

Diagnoses and prescription patterns among users of medications for obstructive airway diseases in Finland.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are common diseases mostly treated in primary care. However, the usage patterns of drugs for obstructive airway diseases (R03 drugs) at the national level are not known. OBJECTIVE: The aims of this study were to describe (1) for which diagnoses each class of R03 drugs were used, (2) the usage pattern of different drug classes for asthma and COPD, and (3) how often these medications were used without a diagnosis of asthma or COPD in Finland. METHODS: We sent questionnaires that included questions on physician-diagnosed asthma and COPD to a random sample of 2000 Finnish subjects who had been dispensed R03 medications in the previous year. Details of R03 medications dispensed were retrieved from national registries. RESULTS: Altogether, 803 subjects (40.6%) responded. Of these, 61.6% had asthma, 5.7% had both asthma and COPD, 5.1% had COPD, and 27.5% had neither asthma nor COPD. Among subjects with asthma or asthma and COPD, inhaled corticosteroids (ICS) were the most frequently dispensed class of drugs (93.7% and 97.8%, respectively). Even among subjects with COPD, ICS were dispensed as frequently (68.3%) as long-acting bronchodilators (70.7%). Antileukotrienes were dispensed mainly to asthmatic individuals only (18.4%) but far less frequently than ICS. The use of theophylline and roflumilast was rare. CONCLUSIONS: R03 medications are dispensed far more frequently for asthma than for COPD and often also for subjects without asthma or COPD. In line with guidelines, asthma is treated mainly with ICS, but there seems to be overuse of ICS for COPD.

Engaging stakeholders to level up COPD care in LMICs: lessons learned from the "Breathe Well" programme in Brazil, China, Georgia, and North Macedonia.

BACKGROUND: Effective stakeholder engagement in health research is increasingly being recognised and promoted as an important pathway to closing the gap between knowledge production and its use in health systems. However, little is known about its process and impacts, particularly in low-and middle-income countries. This opinion piece draws on the stakeholder engagement experiences from a global health research programme on Chronic Obstructive Pulmonary Disease (COPD) led by clinician researchers in Brazil, China, Georgia and North Macedonia, and presents the process, outcomes and lessons learned. MAIN BODY: Each country team was supported with an overarching engagement protocol and mentored to develop a tailored plan. Patient involvement in research was previously limited in all countries, requiring intensive efforts through personal communication, meetings, advisory groups and social media. Accredited training programmes were effective incentives for participation from healthcare providers; and aligning research findings with competing policy priorities enabled interest and dialogue with decision-makers. The COVID-19 pandemic severely limited possibilities for planned engagement, although remote methods were used where possible. Planned and persistent engagement contributed to shared knowledge and commitment to change, including raised patient and public awareness about COPD, improved skills and practice of healthcare providers, increased interest and support from clinical leaders, and dialogue for integrating COPD services into national policy and practice. CONCLUSION: Stakeholder engagement enabled relevant local actors to produce and utilise knowledge for small wins such as improving day-to-day practice and for long-term goals of equitable access to COPD care. For it to be successful and sustained, stakeholder engagement needs to be valued and integrated throughout the research and knowledge generation process, complete with dedicated resources, contextualised and flexible planning, and commitment.

Experiences of patients with advanced COPD affiliated to a cross-sectorial outgoing lung team: A qualitative study.

AIM: To explore experiences of patients affiliated to a cross-sectorial outgoing lung team. BACKGROUND: The outgoing lung team consisted of respiratory nurses from the hospital and community nurses. The lung team offered 24/7 help to patients with advanced chronic obstructive pulmonary disease (COPD) through visits and/or treatment in the patients' home. Affiliation to the lung team reduced both hospitalizations and length of hospital stay due to acute exacerbation of COPD. However, based on questionnaires on health-related quality of life, no significant differences were found between patients affiliated to the lung team and patients receiving usual care. DESIGN: A qualitative interview study. METHODS: In total, 16 patients, aged 61-88 years were interviewed between February 2019 and July 2021. They had been affiliated to the outgoing lung team for 1-3 years. Semi-structured interviews were conducted in the patients' home and audio-recorded after informed consent was obtained. The interviews were transcribed verbatim and analysed, inspired by systematic text condensation by Malterud. FINDINGS: Four themes emerged from the analysis: (1) feeling safe, (2) improvements in living with COPD, (3) avoiding hospitalization and (4) satisfied with staying at home. CONCLUSION: Affiliation to the cross-sectorial outgoing lung team gave the patients peace of mind and improved their ability to live with advanced COPD. The patients preferred contacting the lung team because they could stay at home and receive treatment, and thus avoid hospitalization. IMPACT: The findings from this study support that municipalities should consider implementing an outgoing lung team, as it has the potential to bring several benefits, including improving patient self-management. REPORTING METHOD: The manuscript adhered to Consolidated criteria for reporting qualitative research (COREQ) guideline. PATIENT OR PUBLIC CONTRIBUTION: Patients were interviewed. Additionally, no patient or public contributed to the design or conduction of the study, analysis, or interpretation of the data.

Inhaler use technique course: an effective postgraduate training solution for pharmacists to enhance therapeutic outcomes as part of patient education.

BACKGROUND: Patients with asthma and chronic obstructive pulmonary disease could benefit from education on using inhalers provided by pharmacists. However, pharmacists may have limited competencies, indicating the necessity to implement appropriate postgraduate courses. The study aimed to evaluate an inhaler use course for pharmacists, including its impact on participants' knowledge and satisfaction. METHODS: The study involved 261 pharmacists from community pharmacies and was conducted between September 2019 and March 2021. A pre-post analysis of their knowledge of the topic was applied. Additionally, at the beginning of the course, participants were asked about their educational needs, and at the end, they completed a satisfaction survey. The preferred learning formats indicated by participants were interactive workshops and lectures. RESULTS: As a result of the course, both their actual and self-assessed level of knowledge significantly increased. The percentage of correct answers in the test before the training was 24.4%, while after, it was 84.3% (p < 0.0001). Before the course, their average self-assessed level of knowledge was 52.0%, and after the training, it increased to 90.0% (p < 0.0001). Almost all respondents stated that the course met their expectations. They estimated their satisfaction at 94.0% and the usefulness of the provided information at 98.0%. CONCLUSIONS: Improved preparation of pharmacists resulting from their participation in the course can contribute to providing more professional advice to patients, thereby positively influencing the pharmaceutical care process in community pharmacies.

Effectiveness of a home-based pulmonary rehabilitation maintenance programme: the Rehab2Life study protocol.

Pulmonary rehabilitation (PR) is the bedrock of non-pharmacological treatment for people with COPD. Nonetheless, it is well described in the literature that unless the patient changes his behaviour, the benefits of PR programmes will decline in six to twelve months after finishing the programme. Therefore, maintenance programmes can address the problem of PR programmes' effect loss over time.Community care units can provide multidisciplinary care in the current Portuguese primary health care context. These units have an interdisciplinary team that aims to develop competencies in COPD patients to self-manage the disease.This study aims to test the effectiveness of a 12-month home-based PR programme (Rehab2Life) compared to usual care through a single-blind randomised controlled trial with two parallel groups. The Rehab2Life programme includes two distinct phases. The first is an 8-week PR programme delivered to both groups, and the second is a PR maintenance programme delivered to the intervention group after the initial eight weeks. The control group receive the usual care and regular appointments. The primary outcome is functional capacity, and secondary outcomes are dyspnea, Health-Related Quality of Life (HRQoL), number of exacerbations, symptoms burden, anxiety and depression symptoms, and physical activity.We expect to observe that the home-based PR programme brings clinically relevant benefits to the participants at the end of the first eight weeks and that, at 12 months after the maintenance phase of the programme, benefits are less dissipated than in the control group. We expect to identify the characteristics of the patients who benefit the most from home-based programmes.The trial was registered on 7 April 2022 at ClinicalTrials.gov (NCT05315505).

Examining the Impact of Social Support on Psychological Well-Being Among Canadian Individuals With COPD: Implications for Government Policies.

Chronic obstructive pulmonary disease (COPD) is a significant respiratory disease and is globally ranked as the third leading cause of death. In Canada, the direct healthcare costs associated with COPD are estimated to be $1.5 billion annually. This study utilized quantitative analyses to examine the impact of specific dimensions of social support, namely, guidance, reliable alliance, reassurance of worth, attachment, and social integration within a clinically identified population of individuals with COPD who exhibit symptoms of depression and anxiety. The study was based on the Social Provisions Theory and stress-buffering hypothesis, utilizing large-scale population data from Statistics Canada's 2012 Canadian Community Health Survey (CCHS) Mental Health component. On a national scale, individuals were more likely to report a decreased sense of belonging to a group of friends (social integration) and struggle to depend on others in stressful times (reliable alliance) while experiencing symptoms of anxiety and depression. These findings underscore the potential benefits of integrating peer support, socialization initiatives, and caregiver training into clinical programs designed for individuals with COPD.

The effects of adding a six-month Pilates exercise program to three months of traditional community-based pulmonary rehabilitation in individuals with COPD: a prospective cohort study.

Introduction: Pilates exercise may complement traditional pulmonary rehabilitation in individuals with chronic obstructive pulmonary disease (COPD). The objective was to analyze the effects of adding a six-month Pilates exercise program to a three-month pulmonary rehabilitation for individuals with COPD. Methods: Thirty-five participants with COPD (GOLD B) were assigned to the intervention (n=14) or control (n=21) group. Both groups received an initial three months of a pulmonary rehabilitation program. The intervention group further underwent six months of pilates. Participants were evaluated at baseline and at three, six, and nine months. Lung function and strength of respiratory muscles were defined as primary outcomes. Secondary outcomes included cardiac, physical function, and exacerbation episodes. Results: There were no consistent statistically significant differences between groups for the lung function outcomes (p\<0.05). Maximal inspiratory and expiratory pressure increased significantly at three months in both groups (p\<0.05). It was significantly superior in the intervention group at nine months for maximal inspiratory pressure (p=0.005) and six and nine months for maximal expiratory pressure (p=0.027 and p\<0.001, respectively). Changes in muscle strength (knee extension and handgrip) were comparable between groups (p>0.05), but exercise-induced fatigue and balance were significantly superior in the intervention group at the six- and nine-month follow-ups (p\<0.05). Discussion: Pilates exercise programs may be implemented to augment traditional pulmonary rehabilitation with the goal of improving the strength of respiratory muscles. Conclusion: Adding a Pilates exercise program to pulmonary rehabilitation resulted in superior strength of respiratory muscles, higher resistance to exercise-induced fatigue, and improved balance.

11ß-HSD1 determines the extent of muscle atrophy in a model of acute exacerbation of COPD.

Muscle atrophy is an extrapulmonary complication of acute exacerbations (AE) in chronic obstructive pulmonary disease (COPD). The endogenous production and therapeutic application of glucocorticoids (GCs) have been implicated as drivers of muscle loss in AE-COPD. The enzyme 11 ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) activates GCs and contributes toward GC-induced muscle wasting. To explore the potential of 11ßHSD1 inhibition to prevent muscle wasting here, the objective of this study was to ascertain the contribution of endogenous GC activation and amplification by 11ßHSD1 in skeletal muscle wasting during AE-COPD. Emphysema was induced by intratracheal (IT) instillation of elastase to model COPD in WT and 11ßHSD1/KO mice, followed by vehicle or IT-LPS administration to mimic AE. µCT scans were obtained prior and at study endpoint 48 h following IT-LPS, to assess emphysema development and muscle mass changes, respectively. Plasma cytokine and GC profiles were determined by ELISA. In vitro, myonuclear accretion and cellular response to plasma and GCs were determined in C2C12 and human primary myotubes. Muscle wasting was exacerbated in LPS-11ßHSD1/KO animals compared with WT controls. RT-qPCR and western blot analysis showed elevated catabolic and suppressed anabolic pathways in muscle of LPS-11ßHSD1/KO animals relative to WTs. Plasma corticosterone levels were higher in LPS-11ßHSD1/KO animals, whereas C2C12 myotubes treated with LPS-11ßHSD1/KO plasma or exogenous GCs displayed reduced myonuclear accretion relative to WT counterparts. This study reveals that 11ß-HSD1 inhibition aggravates muscle wasting in a model of AE-COPD, suggesting that therapeutic inhibition of 11ß-HSD1 may not be appropriate to prevent muscle wasting in this setting.

Frequency and severity of respiratory infections prior to COPD diagnosis and risk of subsequent postdiagnosis COPD exacerbations and mortality: EXACOS-UK health care data study.

OBJECTIVE: Little is known about how lower respiratory tract infections (LRTIs) before chronic obstructive pulmonary disease (COPD) are associated with future exacerbations and mortality. We investigated this association in patients with COPD in England. METHODS: Clinical Practice Research Datalink Aurum, Hospital Episode Statistics and Office of National Statistics data were used. Start of follow-up was patient's first ever COPD diagnosis date and a 1-year baseline period prior to start of follow-up was used to find mild LRTIs (general practice (GP) events/no antibiotics), moderate LRTIs (GP events+antibiotics) and severe LRTIs (hospitalised). Patients were categorised as having: none, 1 mild only, 2+ mild only, 1 moderate, 2+ moderate and 1+ severe. Negative binomial regression modelled the association between baseline LRTIs and subsequent COPD exacerbations and Cox proportional hazard regression was used to investigate mortality. RESULTS: In 215 234 patients with COPD, increasing frequency and severity of mild and moderate LRTIs were associated with increased rates of subsequent exacerbations compared with no recorded LRTIs (1 mild adjusted IRR 1.16, 95% CI 1.14 to 1.18, 2+ mild IRR 1.51, 95% CI 1.46 to 1.55, 1 moderate IRR 1.81, 95% CI 1.78 to 1.85, 2+ moderate IRR 2.55, 95% CI 2.48 to 2.63). Patients with 1+ severe LRTI (vs no baseline LRTIs) also showed an increased rate of future exacerbations (adjusted IRR 1.75, 95% CI, 1.70 to 1.80). This pattern of association was similar for risk of all-cause and COPD-related mortality; however, patients with 1+ severe LRTIs had the highest risk of all-cause and COPD mortality. CONCLUSION: Increasing frequency and severity of LRTIs prior to COPD diagnosis were associated with increasing rates of subsequent exacerbations, and increasing risk of all-cause and COPD-related mortality.

Budesonide/formoterol maintenance and reliever therapy versus fluticasone/salmeterol fixed-dose treatment in patients with COPD.

BACKGROUND: Maintenance and reliever therapy (MART) with inhaled corticosteroid (ICS)/formoterol effectively reduces exacerbations in asthma. We aimed to investigate its efficacy compared with fixed-dose fluticasone/salmeterol in chronic obstructive pulmonary disease (COPD). METHODS: Patients with COPD and ≥1 exacerbation in the previous 2 years were randomly assigned to open-label MART (Spiromax budesonide/formoterol 160/4.5 µg 2 inhalations twice daily+1 prn) or fixed-dose therapy (Diskus fluticasone propionate/salmeterol combination (FSC) 500/50 µg 1 inhalation twice daily+salbutamol 100 µg prn) for 1 year. The primary outcome was rate of moderate/severe exacerbations, defined by treatment with oral prednisolone and/or antibiotics. RESULTS: In total, 195 patients were randomised (MART Bud/Form n=103; fixed-dose FSC n=92). No significant difference was seen between MART and FSC therapy in exacerbation rates (1.32 vs 1.32 /year, respectively, rate ratio 1.05 (95% CI 0.79 to 1.39); p=0.741). No differences in lung function parameters or health status were observed. Total ICS dose was significantly lower with MART than FSC therapy (budesonide-equivalent 928 µg/day vs 1747 µg/day, respectively, p<0.05). Similar proportions of patients reported adverse events (MART Bud/Form: 73% vs fixed-dose FSC: 68%, p=0.408) and pneumonias (MART: 5% vs FSC: 1%, p=0.216). CONCLUSIONS: This first study of MART in COPD found that budesonide/formoterol MART might be similarly effective to fluticasone/salmeterol fixed-dose therapy in moderate to severe patients with COPD, at a lower daily ICS dosage. Further evidence is needed about long-term safety.

QRISK3 underestimates the risk of cardiovascular events in patients with COPD.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular disease (CVD). The extent to which the excess CVD risk is captured by risk factors in QRISK, a widely used CVD risk scoring tool, is not well studied. METHODS: We created an incidence cohort of diagnosed COPD patients from the United Kingdom (UK) Clinical Practice Research Datalink GOLD database (January 1998-July 2018). The outcome was a composite of fatal or non-fatal CVD events. Sex-specific age-standardised incidence ratios (SIR) were compared with values for the UK primary-care population. The observed 10-year CVD risk was derived using the Kaplan-Meier estimator and was compared with predicted 10-year risk from the QRISK3 tool. RESULTS: 13 208 patients (mean age 64.9 years, 45% women) were included. CVD incidence was 3.53 events per 100 person-years. The SIR of CVD was 1.71 (95% CI 1.61 to 1.75) in women and 1.62 (95%CI 1.54-1.64) in men. SIR was particularly high among patients younger than 65 years (women=2.13 (95% CI 1.94 to 2.19); men=1.86 (95% CI 1.74 to 1.90)). On average, the observed 10-year risk was 52% higher than QRISK predicted score (33.5% vs 22.1%). The difference was higher in patients younger than 65 years (observed risk 82% higher than predicted). CONCLUSION: People living with COPD are at a significantly heightened risk of CVD over and beyond their predicted risk. This is particularly the case for younger people whose 10-year CVD risk can be >80% higher than predicted. Risk scoring tools must be validated and revised to provide accurate CVD predictions in patients with COPD.

The treatable traits approach to adults with obstructive airways disease in primary and secondary care.

The treatable traits approach is based on the recognition that the different clinical phenotypes of asthma and chronic obstructive airways disease (COPD) are a heterogeneous group of conditions with different underlying mechanisms and clinical manifestations, and that the identification and treatment of the specific clinical features or traits facilitates a personalised approach to management. Fundamentally, it recognises two important concepts. Firstly, that treatment for obstructive lung disease can achieve better outcomes if guided by specific clinical characteristics. Secondly, that in patients with a diagnosis of asthma, and/or COPD, poor respiratory health may also be due to numerous overlapping disorders that can present with symptoms that may be indistinguishable from asthma and/or COPD, comorbidities that might require treatment in their own right, and lifestyle or environmental factors that, if addressed, might lead to better control rather than simply increasing airways directed treatment. While these concepts are well accepted, how best to implement this personalised medicine approach in primary and secondary care within existing resource constraints remains uncertain. In this review, we consider the evidence base for this management approach and propose that the priority now is to assess different prototype templates for the identification and management of treatable traits in both asthma and COPD, in primary, secondary and tertiary care, to provide the evidence that will guide their use in clinical practice in different health care systems.

Endobronchial Valve Treatment Does Not Cause Significant Nickel Deposition in Lung Tissue.

Bronchoscopic lung volume reduction using endobronchial valves (EBVs) is a treatment option for patients with severe emphysema. These EBVs are made out of a nitinol mesh covered by a silicone layer. Nitinol is an alloy of nickel and titanium and is commonly used in implantable medical devices because of its biocompatibility and memory-shape properties. However, there are some concerns that nickel ions can be released from nitinol-containing devices which might cause adverse health effects, especially in patients with a known nickel hypersensitivity. In vitro, it was found that EBV release significant amounts of nickel in the first hours. Our aim was to assess the nickel concentration in lung tissue from a patient who previously underwent EBV treatment but, due to treatment failure, underwent lung volume reduction surgery and to compare this to a reference sample. We found no significant difference in the median nickel concentration between the EBV-treated patient and the non-EBV-treated patient (0.270 vs. 0.328 µg/g, respectively, p = 0.693) and these concentrations were also comparable to previously published nickel concentrations in human lung tissue samples not having any medically implanted devices in the lung. Our results suggest that there is no significant long-term nickel deposition in lung tissue after EBV treatment.

Acceptability and barriers of a GP-physiotherapist partnership in the diagnosis and management of COPD in primary care: A qualitative study.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is commonly diagnosed and managed in primary care but there is evidence that this has been suboptimal, with low confidence expressed in providing interventions requiring behaviour change. The aim of this study was to determine the acceptability of a general practitioner (GP)-physiotherapist partnership in the diagnosis and management of COPD in primary care and to explore the experiences of participants during the implementation of the model. METHODS: Semi-structured interviews were conducted with physiotherapists (n = 3), GPs (n = 2), practice nurses (PNs) (n = 2) and patients (n = 12) who had participated in the InNovaTivE Gp-physiotheRapist pArTnErship for copD (INTEGRATED) trial. We sought to explore participants' views about their experiences and perceived benefits, barriers and facilitators to the implementation of this model of care. Interviews were transcribed, coded and thematically analysed. Synthesis of the data was guided by the Theoretical Domains Framework for clinician interviews and the health belief model for patient interviews. RESULTS: All clinicians felt that this integrated model helped to optimise care for patients with COPD by facilitating evidence-based practice. GPs and PNs valued the physiotherapist's knowledge and skills relating to diagnosis and management, which was reported to complement their own management and improve patient outcomes. Patients reported a sense of empowerment following their appointments and acknowledged improved self-management skills. However, physiotherapists reported many patients were already engaging in positive health behaviours. Responses were mixed on the effectiveness of the model in facilitating teamwork between clinicians with different perspectives concerning management, communication pathways and logistical issues, such as time and room availability, being cited as barriers. CONCLUSIONS: An experienced cardiorespiratory physiotherapist embedded into a small number of primary care practices to work in partnership with GPs for COPD diagnosis and management was acceptable and viewed as beneficial for patients. Barriers relating to logistics and resources remain, which must be addressed to optimise implementation. PATIENT OR PUBLIC CONTRIBUTION: Patient input was obtained from qualitative feedback from a prior study conducted by two authors and was used to refine the model of care to determine the added value of a physiotherapist integrated into the primary care team. This feedback was also used to refine the interview guides utilised in this study determine the acceptability of this model of care. We had health service involvement from the rehabilitation service of the local health district who were directly involved in determining study aims and establishing the project around the priorities for their chronic disease integration service. For example, this project aimed to engage with a less severe patient population in primary care who would benefit from pulmonary rehabilitation. The findings from this study will be used to further tailor the model of care to the needs of the public and patients. TRIAL REGISTRATION: ACTRN12619001127190.